DESCRIPTION (as provided by applicant): The Oklahoma ACE, comprised of 26 investigators from diverse clinical and research backgrounds, partners nationally and internationally known, Oklahoma-based clinical and basic science investigators to collaboratively study diverse aspects of autoimmunity. The central theme of our Oklahoma ACE Basic Science Program is to partner basic investigation with clinical lines of inquiry to understand the biology of autoimmune disease flares to aid diagnosis, clinical trial design, therapeutic development and treatment selection to improve the lives of patients with autoimmune diseases. Through exploration of heightened immune dysregulation closely associated with disease flares at the systemic, cellular and molecular levels, we will identify biologic mechanisms which are important in disease pathogenesis and in clinical disease activity. Our principal project focuses on novel mechanisms of gene expression regulation of TNFAIP3, a potent negative regulator of NF-kB signaling, which has been identified and confirmed as a risk gene for a number of waxing and waning autoimmune diseases. The collaborative project tests hypotheses of regulatory, inflammatory and TNFR exosomal dysregulated immune process association with impending SLE disease flare, as well as provides novel collaborative opportunities to test additional mechanisms of SLE disease activity and to test confirmed flare mechanisms across other autoimmune diseases. Our pilot project will assess mechanisms of multiple sclerosis relapse by examining unique clonal representation through T cell receptor characterization and expansion in CSF and peripheral blood. The overarching goals of our Oklahoma ACE are to understand the pathogenic mechanisms of autoimmune disease flares within and across autoimmune disorders. Our aims foster integration of a multidisciplinary group to study fundamental aspects of autoimmunity, fortify and expand this nucleus through common educational forums, cultivate and expand ACE collaborative scientific interactions, provide the administrative foundation to Oklahoma ACE investigators, and expand integration of our local expertise in genetics, genomics, epigenetics, various aspects of immunology, analytic methodologies and novel clinical trial design to the national ACE Network.